Docarpamine

Docarpamine
Clinical data
Trade names	Tanadopa
Other names	TA-870; TA870; N-(N-Acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine
Routes of; administration	Oral, intravenous
Drug class	Dopamine prodrug; Dopamine receptor agonist
Identifiers
	IUPAC name [4-[2-[[(2S)-2-acetamido-4-methylsulfanylbutanoyl]amino]ethyl]-2-ethoxycarbonyloxyphenyl] ethyl carbonate;
CAS Number	74639-40-0;
PubChem CID	71137;
DrugBank	DB18046;
ChemSpider	64283;
UNII	RPQ57D8S72;
KEGG	D01903;
ChEBI	CHEBI:31513;
ChEMBL	ChEMBL2106351;
CompTox Dashboard (EPA)	DTXSID1057820 ;
Chemical and physical data
Formula	C21H30N2O8S
Molar mass	470.54 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCOC(=O)OC1=C(C=C(C=C1)CCNC(=O)[C@H](CCSC)NC(=O)C)OC(=O)OCC;
	InChI InChI=1S/C21H30N2O8S/c1-5-28-20(26)30-17-8-7-15(13-18(17)31-21(27)29-6-2)9-11-22-19(25)16(10-12-32-4)23-14(3)24/h7-8,13,16H,5-6,9-12H2,1-4H3,(H,22,25)(H,23,24)/t16-/m0/s1; Key:ZLVMAMIPILWYHQ-INIZCTEOSA-N;

Docarpamine (INNTooltip International Nonproprietary Name, JANTooltip Japanese Accepted Name), sold under the brand name Tanadopa, is an orally active dopamine prodrug which is marketed in Japan for the treatment of acute cardiac insufficiency and/or chronic heart failure.^[2]^[3]^[4]^[5]^[6] It is used orally and intravenously.^[1]

In terms of bioactivation, the hydroxyl groups of docarpamine are freed by esterases in the gut and liver and the amino group is freed by γ-glutamyltransferase in the kidney and liver.^[5]^[1]^[7] There is an intermediate, dideethoxycarbonyldocarpamine (DECD), in which the hydroxyl substitutions have been hydrolyzed.^[1] The N-substitution protects the drug from first-pass metabolism by monoamine oxidase (MAO) until it is cleaved into dopamine and allows it to be orally active.^[6]^[7] The drug does not cross the blood–brain barrier or affect the central nervous system even at high doses and hence is peripherally selective.^[1]^[8]^[3] The predicted log P (XLogP3) of docarpamine is 2.9.^[9] It is thought that the therapeutic effects of docarpamine are mediated by activation of peripheral dopamine D₁ receptors.^[3]

Although docarpamine is orally active and can achieve therapeutic levels of dopamine in blood,^[1] relatively high doses and frequent administration of the drug (e.g., 600–750 mg every 8 hours) are required when it is used by this route.^[5]^[4]^[10] Its duration of action orally is described as greater than 4 hours.^[4]

The drug was first described in the scientific literature by 1980.^[2]

References

^ ^a ^b ^c ^d ^e ^f Tekade RK (2020). The Future of Pharmaceutical Product Development and Research. Advances in Pharmaceutical Product Development and Research. Academic Press. p. 207. ISBN 978-0-12-814456-5. Retrieved 13 November 2024.
^ ^a ^b Elks J (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 463. ISBN 978-1-4757-2085-3. Retrieved 13 November 2024.
^ ^a ^b ^c "DOCARPAMINE". Inxight Drugs. Retrieved 13 November 2024.
^ ^a ^b ^c Better O, Greger R, Busch A, Knauf H, Dorup J, Mutschler E, et al. (2012). Diuretics. Handbook of Experimental Pharmacology. Springer Berlin Heidelberg. p. 157. ISBN 978-3-642-79565-7. Retrieved 13 November 2024.
^ ^a ^b ^c Seldin DW, Giebisch GH (1997). Diuretic Agents: Clinical Physiology and Pharmacology. Academic Press. p. 316. ISBN 978-0-08-053046-8. Retrieved 13 November 2024.
^ ^a ^b Finberg J, Youdim M, Riederer P, Tipton K (2013). MAO - The Mother of all Amine Oxidases. Journal of Neural Transmission. Supplementa. Springer Vienna. p. 155. ISBN 978-3-7091-6499-0. Retrieved 13 November 2024.
^ ^a ^b Dhaneshwar SS, Sharma M, Patel V, Desai U, Bhojak J (2011). "Prodrug strategies for antihypertensives". Current Topics in Medicinal Chemistry. 11 (18): 2299–2317. doi:10.2174/156802611797183285. PMID 21671866.
^ Jana S, Mandlekar S, Marathe P (2010). "Prodrug design to improve pharmacokinetic and drug delivery properties: challenges to the discovery scientists". Current Medicinal Chemistry. 17 (32): 3874–3908. doi:10.2174/092986710793205426. PMID 20858214.
^ "Docarpamine". PubChem. Retrieved 13 November 2024.
^ Brinsden PR (2005). A Textbook of In Vitro Fertilization and Assisted Reproduction: The Bourn Hall Guide to Clinical and Laboratory Practice. Taylor & Francis. p. 245. ISBN 978-1-84214-293-6. Retrieved 13 November 2024.

[Tekade2020-1] ^ ^a ^b ^c ^d ^e ^f Tekade RK (2020). The Future of Pharmaceutical Product Development and Research. Advances in Pharmaceutical Product Development and Research. Academic Press. p. 207. ISBN 978-0-12-814456-5. Retrieved 13 November 2024.

[Elks2014-2] Elks J (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 463. ISBN 978-1-4757-2085-3. Retrieved 13 November 2024.

[InxightDrugs-3] "DOCARPAMINE". Inxight Drugs. Retrieved 13 November 2024.

[BetterGregerBusch2012-4] Better O, Greger R, Busch A, Knauf H, Dorup J, Mutschler E, et al. (2012). Diuretics. Handbook of Experimental Pharmacology. Springer Berlin Heidelberg. p. 157. ISBN 978-3-642-79565-7. Retrieved 13 November 2024.

[SeldinGiebisch1997-5] Seldin DW, Giebisch GH (1997). Diuretic Agents: Clinical Physiology and Pharmacology. Academic Press. p. 316. ISBN 978-0-08-053046-8. Retrieved 13 November 2024.

[FinbergYoudimRiederer2013-6] Finberg J, Youdim M, Riederer P, Tipton K (2013). MAO - The Mother of all Amine Oxidases. Journal of Neural Transmission. Supplementa. Springer Vienna. p. 155. ISBN 978-3-7091-6499-0. Retrieved 13 November 2024.

[DhaneshwarSharmaPatel2011-7] Dhaneshwar SS, Sharma M, Patel V, Desai U, Bhojak J (2011). "Prodrug strategies for antihypertensives". Current Topics in Medicinal Chemistry. 11 (18): 2299–2317. doi:10.2174/156802611797183285. PMID 21671866.

[JanaMandlekarMarathe2010-8] Jana S, Mandlekar S, Marathe P (2010). "Prodrug design to improve pharmacokinetic and drug delivery properties: challenges to the discovery scientists". Current Medicinal Chemistry. 17 (32): 3874–3908. doi:10.2174/092986710793205426. PMID 20858214.

[PubChem-9] "Docarpamine". PubChem. Retrieved 13 November 2024.

[Brinsden2005-10] Brinsden PR (2005). A Textbook of In Vitro Fertilization and Assisted Reproduction: The Bourn Hall Guide to Clinical and Laboratory Practice. Taylor & Francis. p. 245. ISBN 978-1-84214-293-6. Retrieved 13 November 2024.

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Docarpamine

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